Department of Material and Biological Chemistry, Faculty of Science, Yamagata University, 1-4-12 Kojirakawa, Yamagata, 990-8560, Japan.
Sci Rep. 2019 Aug 29;9(1):12497. doi: 10.1038/s41598-019-48954-z.
HO permeation through a cell membrane significantly affects living organisms, and permeation is controlled by the physico-chemical nature of lipids and other membrane components. We investigated the molecular relationship between HO permeation and lipid membrane structure using three oxidized lipids. POVPC and PazePC act as intra- and inter-molecular permeation promoters, respectively; however, their underlying mechanisms were different. The former changed the partition equilibrium, while the latter changed the permeation pathway. PoxnoPC inhibited permeation under our experimental conditions via an intra-molecular configuration change. Thus, both intra- and inter-molecular processes were found to control the role of oxidized lipids as inhibitors and promoters towards HO permeation with different mechanisms depending on structure and composition. Here, we identified two independent HO permeation routes: (i) permeation through lipid membrane with increased partition coefficient by intra-molecular configurational change and (ii) diffusion through pores (water channels) formed by inter-molecular configurational change of oxidized lipids. We provide new insight into how biological cells control permeation of molecules through intra- and inter-molecular configurational changes in the lipid membrane. Thus, by employing a rational design for both oxidized lipids and other components, the permeation behaviour of HO and other ions and molecules through a lipid membrane could be controlled.
过氧化物酶体增殖物激活受体（PPAR）是一种核激素受体超家族成员，在调节细胞分化和代谢中发挥重要作用。PPARγ激动剂是一类新型的抗糖尿病药物，能够增强胰岛素敏感性，降低血糖水平。然而，长期使用 PPARγ 激动剂会导致体重增加和水肿等不良反应。为了克服这些问题，研究人员开发了一系列新型的 PPARγ 激动剂，其中一些化合物已经进入临床试验阶段。这些化合物在保持胰岛素敏感性的同时，能够减少体重增加和水肿等不良反应的发生。此外，一些研究表明，PPARγ 激动剂还具有抗炎和抗动脉粥样硬化等作用，可能对心血管疾病的预防和治疗具有重要意义。
